Pharmacogenomics最新文献_第7页

PPARA variant rs1800234 had a dose dependent pharmacogenetics impact on the therapeutic response to chiglitazar. PPARA变异体rs1800234对chiglitazar的治疗反应具有剂量依赖性的药物遗传学影响。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-18 DOI: 10.1080/14622416.2024.2430163

Zhaoxu Geng, Yuanting Zheng, Qian Li, Desi Pan, Xianping Lu, Fei Chen, Ying Zhang, Keying Li, Kaixin Zhou, Leming Shi, You Wang

{"title":"PPARA variant rs1800234 had a dose dependent pharmacogenetics impact on the therapeutic response to chiglitazar.","authors":"Zhaoxu Geng, Yuanting Zheng, Qian Li, Desi Pan, Xianping Lu, Fei Chen, Ying Zhang, Keying Li, Kaixin Zhou, Leming Shi, You Wang","doi":"10.1080/14622416.2024.2430163","DOIUrl":"10.1080/14622416.2024.2430163","url":null,"abstract":"Background: Our objective was to explore the pharmacogenetic impact of three known functional variants in drug target genes and determine whether they can explain the inter-individual variation in therapeutic response.Methods: In a post hoc analysis of data from randomized controlled clinical trials of chiglitazar, we genotyped 481 Chinese patients with T2DM and investigated the association of variants in PPAR genes with the therapeutic outcome separated by dose using linear regression.Results: rs1800234, a gain-of-function variant of PPARA, had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. The C allele was significantly associated with reduced therapeutic response in the 48 mg group, while no significant association was observed in the 32 mg group. In addition, in patients without the C allele, patients treated with 48 mg chiglitazar had a better therapeutic response than those treated with 32 mg chiglitazar. To the contrary, in patients with the C allele, patients treated with 48 mg chiglitazar had a worse therapeutic response than those treated with 32 mg of chiglitazar.Conclusion: The PPARA variant rs1800234 had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. It could help explain the absence of a dose effect of chiglitazar and serve as a potential biomarker for the chosen dose of chiglitazar in the future. In addition, our study provided important reference for the design and clinical application of multi-target drugs.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"605-610"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of genetic variants on fentanyl metabolism in major breast surgery patients: a candidate gene association study. 基因变异对乳腺大手术患者芬太尼代谢的影响：候选基因关联研究。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-20 DOI: 10.1080/14622416.2024.2429365

Shathish Kumar, Kesavan Ramasamy, Harivenkatesh Natarajan, Shravan Venkatraman, Vishnu Eriyat, Pankaj Kundra

{"title":"Impact of genetic variants on fentanyl metabolism in major breast surgery patients: a candidate gene association study.","authors":"Shathish Kumar, Kesavan Ramasamy, Harivenkatesh Natarajan, Shravan Venkatraman, Vishnu Eriyat, Pankaj Kundra","doi":"10.1080/14622416.2024.2429365","DOIUrl":"10.1080/14622416.2024.2429365","url":null,"abstract":"Aim: The study aimed to examine the association of two selected candidate SNPs rs2242480 (CYP3A4) and rs1045642 (ABCB1) with metabolic ratio of plasma norfentanyl to fentanyl concentrations in patients undergoing major breast surgeries.Methods: The retrospective cross-sectional study was done in 257 female patients. DNA extraction, genotyping of selected SNPs, and drug levels measurement were employed.Results: A total of 257 female patients were recruited with no loss to follow up. There was no significant association between the two mentioned SNPs and the metabolic ratio (p value > 0.05). As an exploratory analysis, there was a moderately significant negative correlation between metabolic ratio and pupillary constriction to fentanyl (r = -0.27; p < 0.001). There was also a weak but significant positive correlation between metabolic ratio and time for first analgesia in the postoperative period (r = 0.17; p = 0.01).Conclusion: There was no significant association with the selected candidate SNPs in CYP3A4 and ABCB1 genes and metabolic ratio of norfentanyl to fentanyl in South Indian patients undergoing major breast surgery.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"595-603"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association of DNA methylation, polymorphism and mRNA level of ALAS1 with antituberculosis drug-induced liver injury. ALAS1的DNA甲基化、多态性和mRNA水平与抗结核药物引起的肝损伤的关系

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-09-12 DOI: 10.1080/14622416.2024.2392480

Zhuolu Hao, Bing Han, Xinyue Zhou, Hongkai Jian, Xiaomin He, Lihuan Lu, Meiling Zhang, Hongqiu Pan, Honggang Yi, Shaowen Tang

引用次数: 0

Pharmacogenomics and response to lithium in bipolar disorder. 药物基因组学和双相情感障碍患者对锂的反应。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-25 DOI: 10.1080/14622416.2025.2470605

Pasquale Paribello, Ulker Isayeva, Claudia Pisanu, Alessio Squassina, Mirko Manchia

{"title":"Pharmacogenomics and response to lithium in bipolar disorder.","authors":"Pasquale Paribello, Ulker Isayeva, Claudia Pisanu, Alessio Squassina, Mirko Manchia","doi":"10.1080/14622416.2025.2470605","DOIUrl":"10.1080/14622416.2025.2470605","url":null,"abstract":"Aims: The present review explores the existing evidence on pharmacogenomic tests for prediction of lithium response in the treatment of bipolar disorder. We focused our research article on reports describing findings from genome-wide association studies, polygenic risk scores, and gene expression analyses associated with lithium response.Methods: We conducted a non-systematic review of studies from PubMed/Medline by using terms such as \"pharmacogenomics,\" \"GWAS,\" \"gene expression,\" and \"lithium response.\" Inclusion criteria focused on original research involving human subjects and assessing lithium response outcomes as well as in vitro studies. An extensive pearl-growing strategy was employed to further enlarge the scope of the piece by capitalizing on the knowledge of study authors on the subject.Results: The observed results, albeit promising, remain preliminary in terms of clinical relevance. Machine learning combining genetic and clinical data appears associated with moderate success in predicting lithium responsiveness. Gene expression studies and genome-wide association studies have helped identify possible targets of lithium and have the potential to support target-specific drug research.Conclusions: Pharmacogenomics may support further discoveries in precision medicine further enlarging our understanding of the underlying mechanisms of lithium for its efficacy. However, clinical applications currently appear out of reach in the near future.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"689-706"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Posttransplantation diabetes mellitus (PTDM): pharmacological aspects and genetic predispositions. 移植后糖尿病（PTDM）：药理方面和遗传易感性。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-28 DOI: 10.1080/14622416.2025.2470613

Dorian Chastagner, Hélène Arnion, Clément Danthu, Fatouma Touré, Nicolas Picard

{"title":"Posttransplantation diabetes mellitus (PTDM): pharmacological aspects and genetic predispositions.","authors":"Dorian Chastagner, Hélène Arnion, Clément Danthu, Fatouma Touré, Nicolas Picard","doi":"10.1080/14622416.2025.2470613","DOIUrl":"10.1080/14622416.2025.2470613","url":null,"abstract":"Posttransplantation diabetes mellitus (PTDM) is a form of diabetes developed after solid organ or stem cell transplantation. This condition shares physiopathological traits with type 2 diabetes, including insulin resistance and β-cells dysfunction and its prevalence varies significantly based on the diagnostic criteria used. Immunosuppressive drugs directly contribute to PTDM risk through intricate impacts on glucose regulation, insulin secretion, and inflammation. In addition, modifiable and non-modifiable environmental risk factors are associated with the onset of this condition. This review aims to provide a comprehensive overview of the multifactorial nature of PTDM in order to highlight candidate genes and variants for pharmacogenetic research. An extensive literature search was conducted to identify studies on pharmacological and genetic factors influencing PTDM development. This review stresses the importance of understanding these interactions for improving PTDM management and underscores the need for further research to refine preventive approaches, ultimately enhancing patient outcomes post-transplantation.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"707-718"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer? CYP2D6基因型是否影响羟考酮剂量、药代动力学、疼痛和癌症的不良反应？

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-12-04 DOI: 10.1080/14622416.2024.2430161

Aaron K Wong, Sara Vogrin, Pal Klepstad, Justin Rubio, Brian Le, Jennifer Philip, Andrew A Somogyi

{"title":"Do CYP2D6 genotypes affect oxycodone dose, pharmacokinetics, pain, and adverse effects in cancer?","authors":"Aaron K Wong, Sara Vogrin, Pal Klepstad, Justin Rubio, Brian Le, Jennifer Philip, Andrew A Somogyi","doi":"10.1080/14622416.2024.2430161","DOIUrl":"10.1080/14622416.2024.2430161","url":null,"abstract":"Aims: To examine the associations between CYP2D6 and CYP3A4 polymorphisms, plasma oxycodone and metabolite concentrations, and oxycodone response (dose, pain scores, and adverse effects) in people with pain from advanced cancer.Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects), and blood (pharmacokinetics, DNA). Negative binomial regression and logistic regression were used.Results: Within 33 participants, there were no differences in oxycodone response between CYP2D6 intermediate/poor metabolisers compared to normal metabolisers.Higher plasma noroxycodone and noroxycodone/oxycodone concentration ratios had higher odds of uncontrolled average pain (OR 2.44 (95%CI 1.00-5.95), p = 0.05 and OR 10.48 (95%CI 1.42-77.15), p = 0.02, respectively).Conclusions: There was no observed benefit in CYP2D6 genotyping in oxycodone response, however monitoring noroxycodone and oxymorphone concentrations warrant further examination.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"579-586"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients. 异基因造血干细胞移植患者的 CYP3A4、CYP3A5 和 ABCB1 基因型与他克莫司治疗效果之间的关系。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.2217/pgs-2023-0204

Teresa T Ho, Janelle B Perkins, Rebecca Gonzalez, James Kevin Hicks, Ronald Alvarez Martinez, Katie Duranceau, Brianna North, Jongphil Kim, Jamie K Teer, Jiqiang Yao, Sean J Yoder, Taiga Nishihori, Nelli Bejanyan, Joseph Pidala, Hany Elmariah

{"title":"Association between CYP3A4, CYP3A5 and ABCB1 genotype and tacrolimus treatment outcomes among allogeneic HSCT patients.","authors":"Teresa T Ho, Janelle B Perkins, Rebecca Gonzalez, James Kevin Hicks, Ronald Alvarez Martinez, Katie Duranceau, Brianna North, Jongphil Kim, Jamie K Teer, Jiqiang Yao, Sean J Yoder, Taiga Nishihori, Nelli Bejanyan, Joseph Pidala, Hany Elmariah","doi":"10.2217/pgs-2023-0204","DOIUrl":"10.2217/pgs-2023-0204","url":null,"abstract":"Aim: Successful treatment with tacrolimus to prevent graft versus host disease (GVHD) and minimize tacrolimus-related toxicities among allogeneic hematopoietic cell transplantation (alloHCT) recipients is contingent upon quickly achieving and maintaining concentrations within a narrow therapeutic range. The primary objective was to investigate associations between CYP3A4, CYP3A5 or ABCB1 genotype and the proportion of patients that attained an initial tacrolimus goal concentration following initiation of intravenous (iv.) and conversion to oral administration. Materials & methods: We retrospectively evaluated 86 patients who underwent HLA-matched (8/8) related donor alloHCT and were prescribed a tacrolimus-based regimen for GVHD prophylaxis. Results & conclusion: The findings of the present study suggests that CYP3A5 genotype may impact attainment of initial therapeutic tacrolimus concentrations with oral administration in alloHCT recipients.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"29-40"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing the utility of measurement methods applied in economic evaluations of pharmacogenomics applications. 评估药物基因组学应用经济评估中采用的测量方法的实用性。

IF 2.1 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-01-30 DOI: 10.2217/pgs-2023-0221

Vasileios Fragoulakis, Margarita-Ioanna Koufaki, Korina Tzerefou, Konstantinos Koufou, George P Patrinos, Christina Mitropoulou

引用次数: 0

Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications. 斯里兰卡的药物基因组学：对研究现状和临床影响的全面系统回顾。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-11-14 DOI: 10.1080/14622416.2024.2421743

Priyanga Ranasinghe, Hajanthy Jeyapragasam, Sandamini Liyanage, Nirmala Sirisena, Vajira Hw Dissanayake

{"title":"Pharmacogenomics in Sri Lanka: a comprehensive systematic review of the research landscape and clinical implications.","authors":"Priyanga Ranasinghe, Hajanthy Jeyapragasam, Sandamini Liyanage, Nirmala Sirisena, Vajira Hw Dissanayake","doi":"10.1080/14622416.2024.2421743","DOIUrl":"10.1080/14622416.2024.2421743","url":null,"abstract":"Aim: Pharmacogenomics is emerging in South Asia, including Sri Lanka, with potential to optimize drug therapy and reduce adverse effects. This review evaluates the state of pharmacogenomics research in Sri Lanka, emphasizing population-specific factors to guide future advancements.Materials & methods: A literature search was performed across PubMed/Web-of-Science/SciVerse-Scopus/Embase, and Sri Lanka Journals Online, along with searches for relevant theses in local health repositories/university databases. Studies were categorized into clinical correlational, descriptive or novel assay development studies.Results: Eleven published articles and eight theses were included. One study examined somatic variants (KRAS gene), while all others focused on germline variants. There were two clinical correlational studies: tamoxifen adverse effects and CYP2D6 variants and FTO gene rs9939609 variants and weight gain caused by second-generation antipsychotics. Eight descriptive studies evaluated prevalence of CYP2D6 variants, HLA-B*15:02 allele, KRAS gene mutations and variants related to statin, warfarin and anticancer drug metabolism. Additionally, nine studies developed, validated and tested novel assays for detecting key pharmacogenomically important variants.Conclusion: While pharmacogenomics research in Sri Lanka has made strides, more clinical studies and broader genomic research are needed. Overcoming challenges related to funding, public awareness and regional collaboration is essential to advance personalized medicine and improve therapeutic outcomes in Sri Lanka and South Asia.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"551-567"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TPMT and NUDT15 genotyping, TPMT enzyme activity and metabolite determination for thiopurines therapy: a reference laboratory experience. 硫嘌呤治疗的TPMT和NUDT15基因分型，TPMT酶活性和代谢物测定：参考实验室经验。

IF 1.9 4区医学

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2025-02-16 DOI: 10.1080/14622416.2025.2463866

Sherin Shaaban, Brandon S Walker, Yuan Ji, Kamisha Johnson-Davis

{"title":"TPMT and NUDT15 genotyping, TPMT enzyme activity and metabolite determination for thiopurines therapy: a reference laboratory experience.","authors":"Sherin Shaaban, Brandon S Walker, Yuan Ji, Kamisha Johnson-Davis","doi":"10.1080/14622416.2025.2463866","DOIUrl":"10.1080/14622416.2025.2463866","url":null,"abstract":"Aim: To share the experience of a US national reference laboratory, offering genotyping for TPMT and NUDT15, TPMT enzyme phenotyping and detection of thiopurine metabolites.Methods: Retrospective review of archived datasets related to thiopurines drug therapy including patients' data that underwent TPMT and NUDT15 genotyping, and smaller data sets where genotyping was performed with TPMT enzyme levels (phenotyping) +/- therapeutic drug monitoring (TDM).Results: Thirteen percent of patients had variants in one or both genes tested. Testing for NUDT15 revealed 3.9% additional patients requiring thiopurines dosing recommendations. A correlation between TPMT enzyme activity and TPMT polymorphisms (odds ratio OD = 71.41, p-value <0.001) and between older age and higher enzyme levels (OD = 0.98, p-value = 0.002) was identified. No correlation between sex and TPMT enzyme levels, nor between TPMT genotyping and the level of thiopurine metabolites was found.Conclusion: Adding NUDT15 to TPMT genotyping, identified additional 3.9% patients to benefit from thiopurine dose modifications. A significant correlation between genetic variants in TPMT and TPMT enzyme levels and between age and enzyme levels was established, while no correlation was identified between sex and enzyme levels nor between TPMT variation and thiopurine metabolites. Providers rely more significantly on genotyping only approach, rather than genotyping and phenotyping.","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"679-688"},"PeriodicalIF":1.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0